Abstract: Autoimmune diseases and older people with weakened immune system are a major public health problem; for example, there are about 2 million individuals with RA, i.e. about 1 % of population of USA. Similarly, there are millions of older people with cardiovascular diseases. Better information is needed about the immunoprofiles of older persons. The specific aims of the proposed Phase I studies are to study the age dependent changes in two cohorts of older women: healthy and with cardiac problems. The last group will be divided into two sub-groups: those treated with beta blockers and those not treated. More specifically, the aims are: Aim 1: Develop the supersensitive panel of assays targeting cytokines in older persons; i.e. further improve immunoassays for pro-inflammatory cytokines (TNF-alpha, IFN-gamma, IL-1 beta and IL-6) and anti-inflammatory cytokines (IL-4, IL-10, IL-11); Aim 2: Develop the super-sensitive assay for IL-8 and IL-18; Aim 3: Study the differences in immunoprofiles between women who are healthy and who have cardiac disorders. Phase II will continue the clinical validation of assays developed in the Phase I effort, e.g. we will develop supersensitive assays targeting five additional cytokines. MPD enhanced P-chips (P-chips/MPD) will be used to measure all relevant biomarkers concurrently in a low cost, supersensitive modality. We will optimize the sensitivity, accuracy and user-friendliness of the P-chip/MPD. Concurrent quantitation of cytokines and other low level biomarkers will permit studies of correlation between the immune system and cardiac output.